Disruption of circadian clock linked to accelerated colorectal cancer progression

University of California - IrvineSep 27 2024

Research from the University of California, Irvine has revealed how disruption of the circadian clock, the body's internal, 24-hour biological pacemaker, may accelerate the progression of colorectal cancer by affecting the gut microbiome and intestinal barrier function. This discovery offers new avenues for prevention and treatment strategies.

The study, published online today in the journal Science Advances, offers a more comprehensive understanding of how important changes occur in the function and composition of the gut microbiome when the circadian clock is disturbed in the presence of colorectal cancer.

There is an alarming rise in early-onset colorectal cancer in adults under the age of 50. Circadian misalignment through extended light exposure, late-night meals and other environmental factors could [be] driving these cases. Our study suggests that clock disruption, particularly through lifestyle choices, may play a significant role in gut health and, subsequently, cancer risk."

Selma Masri, corresponding author, associate professor of biological chemistry

Previous research has shown that disturbances to the circadian clock can influence the progression of colorectal cancer, but until now, how the biological clock and cancer impact the gut microbiome was unclear. Using colorectal cancer mouse models, the team found that when the circadian clock is disrupted, the diversity and abundance of gut bacteria change, and this is further exacerbated by cancer development.

Researchers also identified notable alterations in the microbial pathways involved in the metabolism of nucleic acids, amino acids and carbohydrates. These functional changes were linked to reduced levels of intestinal mucus, which normally protects the gut lining from harmful bacteria, suggesting that the circadian clock is crucial for maintaining barrier integrity. Increased permeability of the intestinal lining allows toxins and bacteria to enter the bloodstream, potentially accelerating cancer progression.

"While these findings are important, more work needs to be done," Masri said. "In particular, we now want to know if changes in the timing and abundance of certain gut bacteria could directly lead to colorectal cancer development over time. Long-term studies will be critical in determining whether circadian misalignment drives cancer and how we might prevent it in the future. Deeper insights into how the body's internal clock shapes the gut's ecosystem could pave the way for treatments that not only address cancer but also improve overall gut health."

The study was led by Rachel Fellows, a postdoctoral fellow in biological chemistry. Other team members included Assistant Professors Marcus M. Seldin and Nicholas R. Pannunzio; postdoctoral fellow Sung Kook Chun; graduate students Alisa L. Mahieu, Bridget Fortin and Wei A. Song; and associate specialist Natalie Larson – all from the School of Medicine's Department of Biological Chemistry.

This work was supported by grants from the National Institutes of Health, the Concern Foundation and Johnson & Johnson, among others.